Research letter
Tau protein levels in children do not increase during severe asthma attack-induced hypoxic conditions
S. Hasegawa
, H. Wakiguchi, R. Hirano, F. Okazaki, K. Kudo, T. Ichiyama
Corresponding author
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
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"apellidos" => "Hasegawa" "email" => array:1 [ 0 => "shunji@yamaguchi-u.ac.jp" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "H." "apellidos" => "Wakiguchi" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Hirano" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Okazaki" ] 4 => array:2 [ "nombre" => "K." "apellidos" => "Kudo" ] 5 => array:2 [ "nombre" => "T." "apellidos" => "Ichiyama" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1136 "Ancho" => 1516 "Tamanyo" => 80030 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Serum tau protein concentrations in children who experienced severe asthma attacks versus those in the control subjects. The solid horizontal lines show the mean values, whereas the broken horizontal line shows the mean<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2 SD value for the control (74.4<span class="elsevierStyleHsp" style=""></span>pg/mL).</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">SD: standard deviation.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Children who experience bronchial asthma attacks also experience hypoxic conditions, especially after severe attacks or respiratory failure. Hypoxic conditions during severe asthma attacks may induce neural damage such as axonal damage and neurodegeneration. However, to our knowledge, no studies have been published in this regard. The tau protein plays an important role in the assembly of tubulin monomers into microtubules to form the neuronal microtubule network, maintain microtubule structure and stability, and establish links between microtubules and other cytoskeletal filaments.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The tau protein is mainly produced in the central nervous system (CNS). Brain injuries introduce the tau protein into the cerebrospinal fluid (CSF) and blood; therefore, tau protein levels are markers of axonal damage and neurodegeneration. In this study, we compared the serum tau protein levels in children who experienced severe asthma attacks with those in the control subjects.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The parents of the patients enrolled in this study provided informed consent. Serum samples were obtained from 18 patients admitted to the Department of Pediatrics, Yamaguchi University Hospital, between March 2009 and August 2010 (age range, 7 months to 14 years; mean age, 5.2 years; median age, 5 years; male–female, 13:5; mean SpO<span class="elsevierStyleInf">2</span> on admission, 89.9%) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). We diagnosed bronchial asthma attacks according to the Japanese Pediatric Guidelines for the Treatment and Management of Asthma 2008 (JPGL 2008).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> We also determined asthma attack severity using the JPGL 2008 criteria.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> All of the serum samples were obtained from children who experienced severe asthma attacks at the time of their admission to our hospital. All the patients were given corticosteroids, and 14 required continuous isoproterenol inhalation. In addition, two patients required mechanical ventilation; however, none of these patients displayed neurological sequelae. The control group included 22 healthy children (age range, 1–13 years; mean age, 4.9 years; median age, 5 years; male–female, 12:10). All of the samples were stored at −80<span class="elsevierStyleHsp" style=""></span>°C after collection, and we measured all of the tau protein levels at the same time without freeze thawing.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The serum tau protein levels were measured according to the manufacturer's instructions, using an enzyme-linked immunosorbent assay kit (Immunoassay Kit Human Tau [Total], Invitrogen Corporation, Camarillo, CA, USA) which had a detection limit of 12<span class="elsevierStyleHsp" style=""></span>pg/mL.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The serum tau protein levels (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation [SD]) were 33.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>24.5<span class="elsevierStyleHsp" style=""></span>pg/mL in the children who experienced severe asthma attacks and 29.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22.6<span class="elsevierStyleHsp" style=""></span>pg/mL in the control group (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). No significant differences were observed in the serum tau protein levels for the two groups on analysis using the Mann–Whitney <span class="elsevierStyleItalic">U</span> test (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.503). We established a mean value of the control group<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2 SD as the reference range, and all the samples in both groups fell within the range. In addition, no correlations were observed between the serum tau protein levels and SpO<span class="elsevierStyleInf">2</span> levels in the asthma attack group (data not shown).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Tau protein is reported to be localised in the neuronal axons of the CNS.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Many studies have shown elevated CSF tau protein levels in patients with Creutzfeldt-Jakob disease (CJD), stroke, or Alzheimer disease.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> In addition, some studies have already reported that serum tau protein levels are elevated in patients with acute neurological disorders such as strokes and CJD and are below the detection limit in neurologically healthy individuals.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> We speculate that the hypoxic conditions induced by asthma attacks may cause not only axonal damage but also failure of the blood–brain barrier and that tau protein may appear in the blood and the CSF after axonal damage. The detailed mechanism of how tau protein leaks into the blood remains unclear; however, the serum tau protein levels reflect the CSF levels in patients with CJD.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> We conclude that serum tau protein levels may be a biomarker of brain damage or axonal damage in addition to CSF tau protein levels.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In this study, the serum tau protein levels were not elevated in the children who experienced severe asthma attacks, a finding similar to that seen in the control subjects. All the patients recovered without neurological symptoms after severe asthma attack-induced hypoxic conditions. We treated all of these patients with corticosteroids, continuous isoproterenol inhalation, and mechanical ventilation according to the JPGL criteria. It is most important that the appropriate treatment relieves them from the hypoxic condition as soon as possible. These results suggest that use of the appropriate treatment of severe asthma attacks according to the JPGL criteria can prevent brain damage, axonal damage, neurodegeneration, and destruction of the blood-brain barrier in hypoxic conditions.</p><p id="par0035" class="elsevierStylePara elsevierViewall">This study has a limitation in that there were only two patients with respiratory failure who needed mechanical ventilation. We must, therefore, investigate the serum tau protein levels in more patients with respiratory failure. We also need to examine serum tau levels in patients with neurological sequelae, as none of the patients in the current study displayed such symptoms.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The results of the present study suggest that the hypoxic conditions induced by severe asthma attacks do not induce axonal damage and neurodegeneration in children and that the use of appropriate treatments for asthma attacks in accordance with the JPGL criteria can help prevent neuronal damage.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient's data protection</span><p id="par0045" class="elsevierStylePara elsevierViewall">Confidentiality of data. We have followed the protocols of our work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0050" class="elsevierStylePara elsevierViewall">Right to privacy and informed consent. We have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human subjects and animals in research</span><p id="par0055" class="elsevierStylePara elsevierViewall">The procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None of the authors have conflicts of interest to disclose.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Patient's data protection" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Protection of human subjects and animals in research" ] ] ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1136 "Ancho" => 1516 "Tamanyo" => 80030 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Serum tau protein concentrations in children who experienced severe asthma attacks versus those in the control subjects. The solid horizontal lines show the mean values, whereas the broken horizontal line shows the mean<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2 SD value for the control (74.4<span class="elsevierStyleHsp" style=""></span>pg/mL).</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">SD: standard deviation.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Severe asthma attack (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Control (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>22) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.2 (7 months to 14 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.9 (1–13 years) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender (M:F) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13:5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12:10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SpO<span class="elsevierStyleInf">2</span> on admission (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89.9 (81–94) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corticosteroid: 18Continuous isoproterenol inhalation: 14Mechanical ventilation: 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab458699.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Summary of children with severe asthma attack and control subjects.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tau and taupathies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Robert" 1 => "P.S. Mathuranath" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Neurol India" "fecha" => "2007" "volumen" => "55" "paginaInicial" => "11" "paginaFinal" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17272893" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Japanese pediatric guidelines for the treatment and management of asthma 2008" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Japanese Society of Allergy and Clinical Immunology" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:4 [ "edicion" => "1st ed." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 0 | 1 |
| 2024 October | 9 | 4 | 13 |
| 2024 September | 14 | 2 | 16 |
| 2024 August | 21 | 2 | 23 |
| 2024 July | 14 | 1 | 15 |
| 2024 June | 14 | 3 | 17 |
| 2024 May | 20 | 3 | 23 |
| 2024 April | 36 | 2 | 38 |
| 2024 March | 32 | 5 | 37 |
| 2024 February | 20 | 3 | 23 |
| 2024 January | 19 | 4 | 23 |
| 2023 December | 14 | 6 | 20 |
| 2023 November | 17 | 5 | 22 |
| 2023 October | 14 | 3 | 17 |
| 2023 September | 16 | 2 | 18 |
| 2023 August | 7 | 6 | 13 |
| 2023 July | 25 | 5 | 30 |
| 2023 June | 12 | 4 | 16 |
| 2023 May | 12 | 2 | 14 |
| 2023 April | 12 | 4 | 16 |
| 2023 March | 9 | 3 | 12 |
| 2023 February | 15 | 7 | 22 |
| 2023 January | 12 | 5 | 17 |
| 2022 December | 14 | 5 | 19 |
| 2022 November | 18 | 11 | 29 |
| 2022 October | 19 | 23 | 42 |
| 2022 September | 23 | 7 | 30 |
| 2022 August | 14 | 10 | 24 |
| 2022 July | 18 | 9 | 27 |
| 2022 June | 10 | 5 | 15 |
| 2022 May | 19 | 11 | 30 |
| 2022 April | 20 | 7 | 27 |
| 2022 March | 26 | 6 | 32 |
| 2022 February | 11 | 9 | 20 |
| 2022 January | 18 | 7 | 25 |
| 2021 December | 16 | 16 | 32 |
| 2021 November | 12 | 8 | 20 |
| 2021 October | 22 | 11 | 33 |
| 2021 September | 10 | 11 | 21 |
| 2021 August | 14 | 6 | 20 |
| 2021 July | 6 | 7 | 13 |
| 2021 June | 18 | 9 | 27 |
| 2021 May | 12 | 11 | 23 |
| 2021 April | 27 | 13 | 40 |
| 2021 March | 11 | 11 | 22 |
| 2021 February | 10 | 8 | 18 |
| 2021 January | 12 | 4 | 16 |
| 2020 December | 0 | 2 | 2 |
| 2020 November | 0 | 1 | 1 |
| 2020 August | 0 | 1 | 1 |
| 2020 July | 0 | 1 | 1 |
| 2020 March | 0 | 2 | 2 |
| 2020 February | 0 | 1 | 1 |
| 2019 December | 0 | 1 | 1 |
| 2019 October | 0 | 1 | 1 |
| 2019 September | 0 | 1 | 1 |
| 2019 May | 0 | 7 | 7 |
| 2019 April | 0 | 6 | 6 |
| 2018 March | 1 | 0 | 1 |
| 2018 February | 29 | 2 | 31 |
| 2018 January | 15 | 0 | 15 |
| 2017 December | 28 | 1 | 29 |
| 2017 November | 16 | 3 | 19 |
| 2017 October | 13 | 2 | 15 |
| 2017 September | 6 | 2 | 8 |
| 2017 August | 12 | 1 | 13 |
| 2017 July | 8 | 2 | 10 |
| 2017 June | 17 | 8 | 25 |
| 2017 May | 23 | 17 | 40 |
| 2017 April | 16 | 2 | 18 |
| 2017 March | 13 | 9 | 22 |
| 2017 February | 13 | 4 | 17 |
| 2017 January | 15 | 1 | 16 |
| 2016 December | 20 | 5 | 25 |
| 2016 November | 19 | 4 | 23 |
| 2016 October | 26 | 6 | 32 |
| 2016 September | 13 | 1 | 14 |
| 2016 August | 23 | 6 | 29 |
| 2016 July | 5 | 1 | 6 |
| 2016 June | 15 | 6 | 21 |
| 2016 May | 7 | 1 | 8 |
| 2016 April | 12 | 15 | 27 |
| 2016 March | 13 | 9 | 22 |
| 2016 February | 15 | 9 | 24 |
| 2016 January | 8 | 14 | 22 |
| 2015 December | 10 | 5 | 15 |
| 2015 November | 12 | 1 | 13 |
| 2015 October | 13 | 5 | 18 |
| 2015 September | 19 | 4 | 23 |
| 2015 August | 9 | 2 | 11 |
| 2015 July | 9 | 3 | 12 |
| 2015 June | 7 | 0 | 7 |
| 2015 May | 5 | 3 | 8 |
| 2015 April | 11 | 8 | 19 |
| 2015 March | 10 | 2 | 12 |
| 2015 February | 15 | 5 | 20 |
| 2015 January | 17 | 2 | 19 |
| 2014 October | 0 | 1 | 1 |
| 2014 June | 1 | 0 | 1 |
| 2014 May | 0 | 3 | 3 |
| 2014 March | 34 | 15 | 49 |
| 2014 February | 8 | 8 | 16 |
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